ORMD-0801 is a novel oral human insulin formulated to increase hepatic insulin exposure, and subsequently reduce hepatic glucose production and improve glycemic control, with minimal hypoglycemia risk. In a recently completed randomized, placebo-controlled, multicenter, phase 2b, 12-week study, 354 subjects with T2DM uncontrolled by multiple oral antidiabetic drugs and with HbA1c levels ≥7.5%, received placebo or 8 mg, 16 mg or 32 mg ORMD-0801 capsules up to three times daily. Masked continuous glucose monitoring was performed during a 14-day run-in period and over the last 14 days of treatment. HbA1c levels improved from baseline for most active treatment regimens, with largest improvements recorded in the 8 mg once daily (QD) and twice daily (BID) cohorts. Glucose AUC improved from baseline following 8 mg or 32 mg QD and all tested BID treatments and was most pronounced in patients receiving 8 mg QD at bedtime. Hypoglycemia event rates were low and similar to the placebo arm. Body weight remained stable in all treatment arms and frequency of drug-related adverse events was similar across cohorts.
In summary, ORMD-0801 elicited clinically significant HbA1c reductions in poorly controlled T2DM patients on standard therapies and with mean HbA1c levels >8%, without increasing hypoglycemia rate or weight. The 8 mg QD regimen appears most effective, warranting further studies to confirm the efficacy of this once daily evening dose.
R. Eldor: Advisory Panel; Self; Oramed. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Medtronic, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi. Stock/Shareholder; Self; Oramed. G. Fleming: Consultant; Self; ADOCIA, Biocon, Caladrius Biosciences, Inc., Dance Biopharm Holdings, Inc., Diasome Pharmaceuticals, Inc., Intarcia Therapeutics, MannKind Corporation, NuSirt Biopharma, Inc., Oramed Pharmaceuticals, Sanofi, Tolerion, Inc. J. Neutel: None. K.E. Homer: None. M. Kidron: Employee; Self; Oramed Pharmaceuticals. Stock/Shareholder; Self; Oramed Pharmaceuticals. J. Rosenstock: Research Support; Self; AstraZeneca, Bristol-Myers Squibb, Genentech, Inc., GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Oramed Pharmaceuticals, PegBio Co., Ltd., Pfizer Inc., REMD Biotherapeutics. Other Relationship; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi.